Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.
Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.
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DOI：
10.1186/s12885-017-3509-9
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发表时间：
2017-08-02
期刊：
影响因子：
3.8
通讯作者：
Dittmar T
中科院分区：
文献类型：
--
作者：
Gauck D;Keil S;Niggemann B;Zänker KS;Dittmar T
细胞融合的生物学现象与癌症进展相关，因为已经确定正常细胞×肿瘤细胞融合衍生的杂交细胞可以表现出新的特性，例如增强的转移能力或增加的耐药性，甚至作为可能产生癌症干细胞/起始细胞（CS/IC）的机制。CS/IC已被提出作为表现出干细胞特性的癌细胞，包括（重新）启动肿瘤生长的能力。通过Western blot和激光共聚焦显微镜分析5株来源于M13 SV 1-EGFP-Neo人乳腺上皮细胞和HS 578 T-Hyg人乳腺癌细胞自发细胞融合事件的M13 HS杂交克隆细胞及其亲本细胞的干细胞和EMT相关标志蛋白的表达。通过流式细胞术使用AldeRed荧光染料测定ALDH 1阳性细胞的频率。同时，研究了细胞的集落形成能力以及细胞形成乳腺球的能力。使用3D胶原基质迁移测定分析细胞的迁移活性。M13 HS杂交克隆细胞共表达SOX 9、SLUG、CK 8和CK 14，这些基因在亲本细胞中表达不同。ALDH 1阳性推定干细胞群体的变化在5个杂交种中观察到，范围从1.44%（M13 HS-7）至13.68%（M13 HS-2）。与亲本细胞相比，所有五种杂交克隆细胞都具有增加的但也是独特的集落形成和乳腺球形成能力。M13 HS-4杂交克隆细胞表现出所有杂交体中最高的集落形成能力和第二高的乳腺球形成能力，由此乳腺球的平均直径与亲本细胞相当。相比之下，最大的乳腺球源自M13 HS-2杂交克隆细胞，而这些细胞的乳腺球形成能力与亲本乳腺癌细胞相当。所有的M13 HS杂交克隆表现出间充质表型，除了一个杂交克隆，响应EGF的迁移活性增加。人乳腺上皮细胞和人乳腺癌细胞的融合可以产生具有某些CS/IC特性的杂交克隆细胞，这表明细胞融合可能是表现出CS/IC表型的肿瘤细胞如何起源的机制。本文的在线版本（doi：10.1186/s12885-017-3509-9）包含补充材料，可供授权用户使用。
The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells’ colony forming capabilities as well as the cells’ abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells’ mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS hybrid clones exhibited a mesenchymal phenotype and, with the exception of one hybrid clone, responded to EGF with an increased migratory activity. Fusion of human breast epithelial cells and human breast cancer cells can give rise to hybrid clone cells that possess certain CS/IC properties, suggesting that cell fusion might be a mechanism underlying how tumor cells exhibiting a CS/IC phenotype could originate. The online version of this article (doi:10.1186/s12885-017-3509-9) contains supplementary material, which is available to authorized users.
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影响因子：
11.2
作者：
Hartman ZC;Poage GM;den Hollander P;Tsimelzon A;Hill J;Panupinthu N;Zhang Y;Mazumdar A;Hilsenbeck SG;Mills GB;Brown PH
通讯作者：
Brown PH
影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
3.9
作者：
Jolly, Mohit Kumar;Huang, Bin;Ben-Jacob, Eshel
通讯作者：
Ben-Jacob, Eshel
影响因子：
3.4
作者：
Chang, CC;Sun, W;Trosko, JE
通讯作者：
Trosko, JE
影响因子：
5.6
作者：
Dittmar T;Zänker KS
通讯作者：
Zänker KS